HAEM5:Acute myeloid leukaemia with RBM15::MRTFA fusion: Difference between revisions

| ||''RBM15''(''OTT'') / ''MKL1''(''MAL'')||The majority of both genes retained in the fusion 5’ ''DEK'' and 3’''NUP214''(''CAN'') with the pathogenic derivative being hte der(22).||t(1;22)(p13.3;q13.1)

|This AML subtype is classified based on the presence of a t(1;22)(p13.3;q13.1), which results in fusion of ''RBM15''(''OTT'') at 1p13.3 [hg38] and ''MKL1''(''MAL'') at 22q13.1 [hg38] with variable breakpoints<ref name=":1">{{Cite journal|last=Ma|first=Z.|last2=Morris|first2=S. W.|last3=Valentine|first3=V.|last4=Li|first4=M.|last5=Herbrick|first5=J. A.|last6=Cui|first6=X.|last7=Bouman|first7=D.|last8=Li|first8=Y.|last9=Mehta|first9=P. K.|date=2001|title=Fusion of two novel genes, RBM15 and MKL1, in the t(1;22)(p13;q13) of acute megakaryoblastic leukemia|url=https://www.ncbi.nlm.nih.gov/pubmed/11431691|journal=Nature Genetics|volume=28|issue=3|pages=220–221|doi=10.1038/90054|issn=1061-4036|pmid=11431691}}</ref><ref name=":3">WHO Classification of Tumours Editorial Board, eds, WHO Classification of Tumours, Haematolymphoid Tumours, 5th edition, IARC Press:Lyon, 2024.  Online at: [https://tumourclassification.iarc.who.int/welcome/ WHO Classification of Tumours].</ref><ref>{{Cite journal|last=Khoury|first=Joseph D.|last2=Solary|first2=Eric|last3=Abla|first3=Oussama|last4=Akkari|first4=Yassmine|last5=Alaggio|first5=Rita|last6=Apperley|first6=Jane F.|last7=Bejar|first7=Rafael|last8=Berti|first8=Emilio|last9=Busque|first9=Lambert|date=2022-07|title=The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Myeloid and Histiocytic/Dendritic Neoplasms|url=https://pubmed.ncbi.nlm.nih.gov/35732831|journal=Leukemia|volume=36|issue=7|pages=1703–1719|doi=10.1038/s41375-022-01613-1|issn=1476-5551|pmc=9252913|pmid=35732831}}</ref>.  Although both reciprocal fusions are expressed, the ''RBM15''-''MKL1'' fusion on the derivative chromosome 22 is the candidate oncoprotein because it contains all of the putative functional domains of both proteins<ref name=":1" />. Typically the ''RBM15''-''MKL1'' fusion presents as the sole abnormality<ref name=":3" />.The t(1;22) occurs in <1% of all AML cases and 10-1% of pediatric acute megakaryoblastic leukemia cases (REFERENCE). It is most frequent in infants (<6 months old) and young children (<3 years old) with Down syndrome and has a female predominance. Rarely it occurs in adults (REFERENCES). Translocation-confirmed cases with <20% blasts on aspirate smears should be correlated with the biopsy to exclude an artificially low count due to marrow fibrosis, and then if the blasts remain low, followed closely to monitor for development of more definitive evidence for AML (such as the occurrence of extramedullary disease or myeloid sarcoma)<ref name=":3" />. This translocation was originally associated with poor prognosis but some studies demonstrate good response to intensive chemotherapy with long disease-free survival<ref name=":3" />.  Two retrospective studies in 2015 and 2016 of non-Down syndrome pediatric AMKL patients found that the ''RBM15''-''MKL1'' fusion was present in 12% and 13.7% of cases, was associated with significantly younger onset, and was considered to have a relative risk classification of intermediate or standard<ref name=":2">{{Cite journal|last=Inaba|first=Hiroto|last2=Zhou|first2=Yinmei|last3=Abla|first3=Oussama|last4=Adachi|first4=Souichi|last5=Auvrignon|first5=Anne|last6=Beverloo|first6=H. Berna|last7=de Bont|first7=Eveline|last8=Chang|first8=Tai-Tsung|last9=Creutzig|first9=Ursula|date=2015|title=Heterogeneous cytogenetic subgroups and outcomes in childhood acute megakaryoblastic leukemia: a retrospective international study|url=https://www.ncbi.nlm.nih.gov/pubmed/26215111|journal=Blood|volume=126|issue=13|pages=1575–1584|doi=10.1182/blood-2015-02-629204|issn=1528-0020|pmc=4582334|pmid=26215111}}</ref><ref>{{Cite journal|last=de Rooij|first=Jasmijn D. E.|last2=Masetti|first2=Riccardo|last3=van den Heuvel-Eibrink|first3=Marry M.|last4=Cayuela|first4=Jean-Michel|last5=Trka|first5=Jan|last6=Reinhardt|first6=Dirk|last7=Rasche|first7=Mareike|last8=Sonneveld|first8=Edwin|last9=Alonzo|first9=Todd A.|date=2016|title=Recurrent abnormalities can be used for risk group stratification in pediatric AMKL: a retrospective intergroup study|url=https://www.ncbi.nlm.nih.gov/pubmed/27114462|journal=Blood|volume=127|issue=26|pages=3424–3430|doi=10.1182/blood-2016-01-695551|issn=1528-0020|pmc=5161011|pmid=27114462}}</ref>.  However, the majority of studies showed this to be a high-risk disease compared with pediatric AMKL without t(1;22). Careful supportive care is likely required to prevent early death related to intensive chemotherapy<ref>{{Cite journal|last=Creutzig|first=Ursula|last2=Zimmermann|first2=Martin|last3=Reinhardt|first3=Dirk|last4=Dworzak|first4=Michael|last5=Stary|first5=Jan|last6=Lehrnbecher|first6=Thomas|date=2004|title=Early deaths and treatment-related mortality in children undergoing therapy for acute myeloid leukemia: analysis of the multicenter clinical trials AML-BFM 93 and AML-BFM 98|url=https://www.ncbi.nlm.nih.gov/pubmed/15514380|journal=Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology|volume=22|issue=21|pages=4384–4393|doi=10.1200/JCO.2004.01.191|issn=0732-183X|pmid=15514380}}</ref>, especially considering the very young age of patients with this AML subtype; differences in such care may cause the lack of prognostic consistency<ref name=":2" />.